Hypokalemic periodic paralysis (HOKPP) is characterized by episodes of muscle paralysis associated with a fall in blood potassium levels (hypokalemia).[1] Episodes typically involve a temporary inability to move muscles in the arms and legs.[2] The first attack usually occurs in childhood or adolescence. Attacks can last for hours or days, and the frequency of attacks varies among people with HOKPP. The frequency is usually highest between the ages of 15 and 35, and then decreases with age. Some people with HOKPP also develop late-onset proximal myopathy.[3]

HOKPP can be caused by mutations in the CACNA1S, SCN4A, or KCNJ18gene. Inheritance is autosomal dominant. Treatment varies depending on the intensity and duration of attacks. Minor attacks may go away on their own, while treatment for moderate or severe attacks may involve taking potassium salts or intravenous (IV) potassium.[3]

HOKPP is characterized by attacks of muscle weakness or loss of muscle movement (paralysis) that come and go. The weakness or paralysis is most commonly located in the shoulders and hips, affecting the muscles of the arms and legs. Muscles of the eyes and those that help you breathe and swallow may also be affected.[4] While muscle strength is usually regained between attacks, repeated episodes can lead to persistent muscle weakness later in life.[2][4]

Attacks usually begin in childhood or adolescence, and the frequency of attacks varies. Some people have attacks every day, while others have them once a year. Attacks usually last at least a few hours, to sometimes days.[4][3] Attacks can occur without warning or they may be triggered by factors such as carbohydrate-rich meals and rest after exercise.[3]

Last updated: 6/12/2017

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition.
Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency).
Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

HOKPP can be caused by mutations in any of at least 3 known genes: CACNA1S, SCN4A, or KCNJ18. All three of these genes give the body instructions to make parts of ion channels that are primarily expressed in skeletal muscle cells.[3] Muscle contractions are triggered by the flow of ions into muscle cells. Mutations that cause HOKPP affect the usual structure or function of ion channels, impairing their ability to regulate the flow of ions into muscle cells. This, in turn, reduces the ability of skeletal muscles to contract, causing the weakness and paralysis associated with HOKPP.[2]

Not all people with a clinical diagnosis of HOKPP are found to have a mutation in one of the genes mentioned above. This suggests that other, yet unidentified genes may also be responsible for the condition.[3]

Hypokalemic periodic paralysis (HOKPP) is inherited in an autosomal dominant manner.[3] This means that having a change (mutation) in only one copy of one of the responsible genes in each cell is enough to cause symptoms of the condition.

In most cases, an affected person inherits the mutated gene from an affected parent. However, inheritance from a parent may sometimes be "masked" by a parent not having symptoms. This is because not all people with a mutation in a gene responsible for HOKPP develop symptoms of the condition - a phenomenon known as reduced penetrance. About 10% of males with a mutation do not develop symptoms, and a higher percentage of females do not develop symptoms. The penetrance of HOKPP appears to depend on the specific gene and mutation responsible for the condition, and the gender of the person with the mutation. For example, one reported mutation in the CACNA1S gene appears to be fully penetrant in males (100% develop symptoms) but non-penetrant in females (none develop symptoms). Identifying the responsible gene and mutation in an affected person may therefore help to assess risks to other family members.[3]

It is also possible for a disease-causing mutation to occur for the first time in a person with no family history of HOKPP. This is called a de novo mutation. The proportion of cases caused by a de novo mutation is unknown.[3]

Regardless of whether a mutation that causes an autosomal dominant condition is de novo or inherited, each child of a person with a mutation has a 50% chance to inherit that mutation.

a family history consistent with autosomal dominant inheritance. The diagnosis cannot be established by clinical findings alone in the absence of a known family history of the condition.

Various types of tests including blood tests, urine tests, and/or electromyograms may be used to differentiate between primary HOKPP and other possible causes of symptoms.[3]

Of all individuals who meet diagnostic criteria and have genetic testing, approximately 60% have mutations in the CACNA1Sgene, approximately 20% in the SCN4A gene, and approximately 3.5% in the KCNJ18 gene. No other genes have yet been found to cause HOKPP, suggesting that other, unidentified genes may be responsible for the condition.[3]

Last updated: 6/12/2017

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment of HOKPP may lead to a significant decrease in the number of episodes and prevent muscle weakness in some people.[1][4] However, a progressive proximal myopathy ultimately develops in most people with HOKPP, usually becoming apparent after the age of 50 years as attacks of paralysis lessen. The myopathy is generally worst in muscles of the pelvis as well as the proximal upper and lower extremities (the muscles of the arms and legs closest to the trunk). The severity of the myopathy varies, as some may be only mildly affected and others may be severely disabled.[5] Several deaths in people with HOKPP have been reported, mostly related to aspiration pneumonia or inability to clear secretions.[6]

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Hypokalemic periodic paralysis. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Hypokalemic periodic paralysis. This website is maintained by the National Library of Medicine.

MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.

Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.

Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

PubMed is a searchable database of medical literature and lists journal articles that discuss Hypokalemic periodic paralysis. Click on the link to view a sample search on this topic.

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My 26 year old son has been recently diagnosed with hypokalemic periodic paralysis. No other family members including myself, his mother, or his sister have shown any symptoms of this. He had not shown any symptoms until the past 6 months.
Is it likely his sister will also have this disorder? Is it likely my brother's children will be affected? There is no record of any parents or other family members being affected.
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I have hypokalemic periodic paralysis and plan on having children soon. Could my condition worsen during pregnancy and/or childbirth? Does this condition affect the development of a fetus? How rare is this condition in African Americans?
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